Lung cancer remains the major cause of cancer death among both males and females. Recognition of the expression of one or more neoplastic antigens in advance of clinical cancer opens several potential therapeutic alternatives.
Four types of lung cancer are found in humans: squamous, adeno, small cell, and large cell. Each tumor expresses specific differentiation features or surface phenotype determinants, all of which distinguish these cells from normal cells. The development of monoclonal antibody diagnostic techniques has greatly enhanced the production of reagents capable of differentiating normal cells from cancer cells and differentiating types of cancer cells from other cancer cells.
Sputum cytology screening of bronchial epithelial-cell morphologic atypia has not so far led to frequent, early-stage lung cancer detection and cure. This was most convincingly demonstrated in a large three-institution study sponsored by the National Cancer Institute, as reported in Am Rev Respir Dis 130:545-549, 555-560, 561-565, and 565-570, 1984. As part of this study to determine whether the addition of sputum cytology screening could significantly enhance lung cancer detection and reduce lung cancer mortality when compared to radiographic screening alone, the Johns Hopkins Lung Project obtained expectorated sputum cytology specimens and chest radiographs serially over a period of from five to eight years from male smokers, 45 years of age and older. From 1973 to 1977, 10,384 of these high risk individuals were recruited. Half were randomized to receive cytology screening plus chest radiography, and the other half were screened by radiography alone. Cytology screening was found to be insufficiently sensitive, there being too many false negatives.
Several mouse monoclonal antibodies produced against antigens on small cell and non-small cell human lung cancer have been used in immunohistochemical assays to study tumor biology, lung cancer immunolocalization, and to give clues to tumor ancestry. The antigens recognized by these antibodies are expressed on a variety of tumors as well as normal fetal tissue. As summarized in the proceedings of the First International Workshop on Antigens of Small Cell Lung Cancer, Souhami et al., Lancet 2(8554): 325-6, 1987, there are nearly 100 monoclonal antibodies being investigated to study small cell and non-small cell cancer of the lung. This workshop supported central registry coding of antibodies followed by blinded staining of a variety of normal and neoplastic tissues. Statistical analyses of the results led to a definition of clusters of reactivity which suggested similar antigenic determinants were being recognized by two or more monoclonal antibody reagents. None of the antigens studied were either specific for small cell lung cancer or were universally present on all small cell lung cancer specimens studied.
Rather than strict tumor markers, these antigenic determinants may be markers of differentiation. Progressive neoplastic differentiation in carcinogen exposed individuals may lead to an increased expression of these markers in the bronchial epithelium before overt development of a pulmonary neoplasm.
Mulshine et al, in U.S. Pat. No. 4,569,788, disclose monoclonal antibodies which can be used to detect human non-small cell lung cancer and distinguish this type of cancer from all other types of lung cancer and normal tissue cells. These two antibodies may be utilized in kit form to distinguish non-small cell lung cancer form other forms of lung cancer by testing the tumor tissue.
Among other monoclonal antibodies used to determine cancer in humans is a monoclonal antibody of the IgM class, U.S. Pat. No. 4,683,200, to Hirohashi et al. The monoclonal antibody disclosed in this patent is reactive with human cancers of the lung, and can be used for serum diagnosis of a patient suffering from cancer.
Loor et al, U.S. Pat. No. 4,690,890, disclose a process for detecting at least two antigens using an immunometric dual sandwich assay containing an effective amount of at least one monoclonal antibody against each antigen. This technique is particularly useful for assaying for prostatic acid phosphatase and prostate antigen.
Tanswell et al, U.S. Pat. No. 4,624,930, disclose a process for determining the presence of polyvalent antigens by incubation with three receptors wherein the first receptor is a complete antibody or an antibody covalently bound to hapten, the second receptor is an antibody which is capable of binding with only a part of the first receptor, and the third receptor, which must not cross-react with the second receptor, can be an antibody capable of binding with the antigen, which is obtained from an animal species different from that from which the first receptor is obtained.